The overall objective of this grant proposal is to develop and assess a system to enhance the rational and personalized application of antiplatelet therapy for patients undergoing percutaneous coronary intervention (PCI, or coronary angioplasty and stenting). This proposal describes a 5 year research and training program designed to provide the candidate, Robert Yeh, the necessary skills and experience to develop an independent academic research career in the conduct of translational cardiovascular outcomes research. Candidate: Dr. Yeh received an MSc in health policy from the London School of Economics, an MD from Harvard Medical School, and has completed clinical training in internal medicine (MGH), cardiology (UCSF) and interventional cardiology (MGH). He is now a junior faculty member at the Massachusetts General Hospital with 75% protected time to conduct clinical research. While he has successfully been involved with epidemiologic and secondary data analysis, Dr. Yeh will pursue additional training in the areas of decision analysis, clinical trial conduct and implementation research, and bioinformatics - training which will allow him to translate outcomes research findings into novel interventions which improve patient health. The candidate's long-term goal is to become an R01-funded investigator in the applied outcomes research that has a broad impact on population health. Environment: The candidate will be mentored by Dr. Laura Mauri (Primary Mentor), Associate Professor of Medicine at HMS and chief scientific officer of the Harvard Clinical Research Institute (HCRI), and Dr. Sharon- Lise Normand (Co-Mentor), Professor of Health Care Policy at HMS and Vice Chair of the Patient-Centered Outcomes Research Institute's Methods Committee. Both are internationally recognized leaders in their respective fields, and provide complementary expertise relevant to the research and training of the candidate. Dr. Mauri has an established track record of successfully leading practice-changing multicenter clinical trials in interventional cardiology, including the NIH/FDA/Industry-sponsored Dual Antiplatelet Theray (DAPT) Study. She has mentored several cardiovascular clinical investigators, including those that have received K awards and R01 funding. Dr. Normand has successfully mentored a large number of successful academic investigators, and is an internationally recognized expert in outcomes and comparative effectiveness research methods used in this proposal. The combined resources of several Harvard Medical School institutions, including HCRI, the Department of Health Care Policy, and the MGH Heart Center will support a rich and productive environment for Dr. Yeh's career development through a combination of didactic training, seminars, weekly research meetings, and conference presentations. Research: In the current era of invasive management of coronary artery disease, balancing the tradeoff between ischemic events and bleeding complications has become integral to decisions regarding the type and duration of antiplatelet therapy in patients undergoing coronary intervention. In Aim 1, multivariable logistic regression will be used to develop models that can predict bleeding and ischemic events in patients after PCI depending on antiplatelet strategy, using data from the DAPT Study, the largest PCI clinical trial conducted to date, and the Massachusetts PCI Registry, a comprehensive longitudinal registry of patients undergoing coronary intervention. Models that can predict treatment benefit or harm associated with specific strategies will be developed. In Aim 2, decision analysis methods will be employed to enhance these models such that the treatment strategy which is predicted to maximize patient benefit can be identified for all patients, and associated uncertainty in this determination can be assessed. In Aim 3, these tools will be integrated into a novel software application that can execute multivariable risk predictions at the point of care within the MGH cardiac catheterization laboratory. These tools will be used as clinical decision aids, and tested in a prospective randomized clinical trial to determine whether such interventions can enhance clinical decision making. The research will demonstrate how the end products of outcomes research can be translated into innovative interventions that can personalize medical decisions and ultimately improve patient care.